Fluorescent p-substituted-phenyl-imidazolo-cytidine analogues

Abstract

The synthesis and spectral properties of modified cytidine analogues are described here. To confer fluorescent properties, the cytidine fluorophore was extended by a cinnamyl moiety at the cytidine 5-position, (analogues 1a–c), or extended by a phenyl-imidazolo ring, (analogues 3a–d). Those compounds were synthesized via the Suzuki–Miyaura coupling reaction and via condensation of 5-amino-cytidine with p-substituted benzaldehydes, respectively. All analogues were fluorescent in the blue region (λem: 402–436 nm). Among the above mentioned analogues, p-CF3–phenyl-imidazolo-cytidine, 3d, was found to be a promising fluorescent probe, exhibiting a quantum yield 7000-fold larger than cytidine (Φ=0.617) and a red-shift of ca. 108 nm of maximum emission (411 nm). Its retained Watson–Crick hydrogen bonding face allows 3d to base-pair specifically with guanosine, similar to cytidine. In addition, phenyl-imidazolo-cytidine analogues prefer anti conformation and the C3′-endo (N) sugar puckering. These properties make 3d an attractive fluorescent probe for potential use in the various facets of nucleic acid chemistry.